Post on 26-Mar-2020
FACTORS PROMOTING ANTHELMINTIC RESISTANCE European Medicines Agency
June 13, 2016
Edwin ClaereboutLaboratory for Parasitology, Faculty of Veterinary Medicine,
Ghent University, Belgium
• Contents– Important helminth parasites in livestock and horses– Prevalence of anthelmintic resistance– Factors promoting anthelmintic resistance– Sustainable use of anthelmintics
Cooperia spp.Ostertagia ostertagiDictyocaulusviviparusFasciola hepatica
Nematodirus helvetianusTeladorsagia circumcinctaHaemonchus contortusFasciola hepatica
Ascaris suumTrichuris suis
Small strongylesParascaris equorumOxyuris equi
• Imidothiazoles (levamisole) • Tetrahydropyrimidines (pyrantel)• Benzimidazoles• Macrocyclic lactones• Amino-‐acetonitril derivates (monepantel)• Spiroindoles (derquantel)• Phenol and salicylanilide derivates (closantel,
nitroxinil, oxyclosanide)
•Limited introduction of new anthelmintics•No real alternative control strategies
CRUCIAL TO MAINTAIN THE EFFECTIVENESS OF THESE DRUGS
Anthelmintic resistance in animalsHost Species Benzimidazoles Levamisole Macrocyclic
lactonesOther
Cattle Cooperia spp.Haemonchus placeiOstertagia ostertagiTrichostrongylus axei
XXXX
XX
XXX
Sheep & Goats
Haemonchus contortusTeladorsagia spp.Trichostrongylus spp.Nematodirus spp.
XXXX
XXX
XXX
MonepantelMonepantelMonepantel
Horses CyathostominaeParascaris equorum
XX
Pyrantel
Pigs Oesophagostomum spp. x x x
Dogs Ancylostoma caninum Pyrantel
ARGENTINA
URUGUAYBRAZIL
PARAGUAY
MEXICO
UNITED STATESVENEZUELA
INDIA
PAKISTAN
AUSTRALIA
NEW ZEALAND
BANGLADESH
SOUTH AFRICA
EUROPEAN UNIONTURKEY
ZIMBABWE
Cameroon
NIGERIA
KENYA
Adapted from ‘Anthelmintics and Resistance: A Review’ (Novartis)
Photos courtesy of Dr Neil Sargison (Edinburgh Vet School)
‘Drug resistance in nematodes: a paper tiger or a real problem ?’(Waller, 1985)
2001 2003
Case study of a cattle farm:
Effic. D212006 73,02007 40,02008 0,0
Surviving species: Cooperia oncophora
Ivermectin efficacy:
El-‐Abdellati et al., 2010. Veterinary Parasitology 171, 167-‐171
-‐ Anthelmintic resistance-‐ Quality of the products-‐ Underdosing-‐ Drug formulation (injectable, oral, pour-‐on)-‐ Sensitivity of the detection technique-‐ …
Development of anthelmintic resistance
Refugia = proportion of helminth population that is not under selection pressure
Factors promoting anthelmintic resistance• Few published studies
– Mostly observational studies– Few clinical studies– Systematic review and meta-‐analysis (sheep) :
Factors promoting anthelmintic resistance• Introduction of anthelmintic resistance (no quarantine treatment)
– Suter et al., 2004, 2005• Frequent treatments*
– Treatment interval close to pre-‐patent period
Falzon et al., 2014. Prev Vet Med 117(2):388-‐402 (sheep)Suarez & Christel, 2014. Rev Bras Parasitol Vet 23(2):129-‐35 (cattle)
Factors promoting anthelmintic resistance• Long term use of the same anthelmintic class vs. rotation?
– Leignel et al., 2010• Under-‐dosing
– No weighing prior to treatment– Treating goats with sheep dose– ‘Tailing off’ of long acting formulation (e.g. intraruminal bolus)NS-‐> Survival of worms with heterozygous resistance alleles.
Falzon et al., 2014. Prev. Vet. Med. 117(2):388-‐402
Factors promoting anthelmintic resistance• Lack of efficacy testing• Treatment when environmental refugia is low
– Treating ewes at lambing (Haemonchus contortus)– Treating during draught period– Treat and move to clean pasture (‘Dose and move’, ‘Drench-‐and-‐shift’) NS
Falzon et al., 2014. Prev. Vet. Med. 117(2):388-‐402
Factors promoting anthelmintic resistance• Mixed-‐species grazing? NS
– Protective or risk factor?
• Flock/herd size? NS
Falzon et al., 2014. Prev. Vet. Med. 117(2):388-‐402
Sustainable use of anthelmintics• Avoid risk factors mentioned above
– SCOPS (www.scops.org.uk)• Reduced number of treatments (‘targeted treatments’)
– Monitoring infection levels (FEC, pepsinogen, antibodies)– Monitoring production (weight, milk)
• Treatment of individual animals (‘targeted strategic treatments’) – Monitoring infection levels (FEC, milk antibodies)– Monitoring production (weight, milk)
• Combination anthelmintics?• Development of alternative control methods
– Vaccines – Anthelmintic plant components (condensed tannins)
• Development of economic farm system models with integrated worm control (e.g. ParaCalc®)
Integrated control of parasites in livestock
Epidemiology
• Monitoring parasite infections•Identify risk factors
Pharmacology, Parasitology
• New drugs•Sustainable use of existing antiparasitics
Farm management
• Financial impact of infection & treatment
Economics
Immunology & vaccinology
• Vaccines
Genetics
• Resistant cattle•Identification of susceptible animals
improved managementof parasitic infections
more effective treatment
vaccination
Solution = integrated parasite control